Journal articles: 'Polymyxin B administration'

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Vaara, Martti, Timo Vaara, Janis Kuka, Eduards Sevostjanovs, Solveiga Grinberga, Maija Dambrova, and Edgars Liepinsh. "Excretion of the Polymyxin Derivative NAB739 in Murine Urine." Antibiotics 9, no. 4 (March 27, 2020): 143. http://dx.doi.org/10.3390/antibiotics9040143.

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Extremely multiresistant strains of Enterobacteriaceae are emerging and spreading at a worrisome pace. Polymyxins are used as the last-resort therapy against such strains, in spite of their nephrotoxicity. We have previously shown that novel polymyxin derivatives NAB739 and NAB815 are less nephrotoxic in cynomolgus monkeys than polymyxin B and are therapeutic in murine Escherichia coli pyelonephritis at doses only one-tenth of that needed for polymyxin B. Here we evaluated whether the increased efficacy is due to increased excretion of NAB739 in urine. Mice were treated with NAB739 and polymyxin B four times subcutaneously at doses of 0.25, 0.5, 1, 2, and 4 mg/kg. In plasma, a clear dose–response relationship was observed. The linearity of Cmax with the dose was 0.9987 for NAB739 and 0.975 for polymyxin B. After administration of NAB739 at a dose of 0.25 mg/kg, its plasma concentrations at all tested time points were above 0.5 µg/mL while after administration at a dose of 0.5 mg/kg its plasma concentrations exceeded 1 µg/mL. The Cmax of NAB739 in plasma was up to 1.5-times higher after single (first) administration and up to two-times higher after the last administration when compared to polymyxin B. Polymyxin B was not detected in urine samples even when administered at 4 mg/kg. In contrast, the concentration of NAB739 in urine after single administration at a dose of 0.25 mg/kg was above 1 µg/mL and after administration of 0.5 mg/kg its average urine concentration exceeded 2 µg/mL. At the NAB739 dose of 4 mg/kg, the urinary concentrations were higher than 35 µg/mL. These differences explain our previous finding that NAB739 is much more efficacious than polymyxin B in the therapy of murine E. coli pyelonephritis.

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Iudin, Dmitrii, Natalia Zashikhina, Elena Demyanova, Viktor Korzhikov-Vlakh, Elena Shcherbakova, Roman Boroznjak, Irina Tarasenko, et al. "Polypeptide Self-Assembled Nanoparticles as Delivery Systems for Polymyxins B and E." Pharmaceutics 12, no. 9 (September 11, 2020): 868. http://dx.doi.org/10.3390/pharmaceutics12090868.

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Polymyxins are peptide antibiotics that are highly efficient against many multidrug resistant pathogens. However, the poor stability of polymyxins in the bloodstream requires the administration of high drug doses that, in turn, can lead to polymyxin toxicity. Consequently, different delivery systems have been considered for polymyxins to overcome these obstacles. In this work, we report the development of polymyxin delivery systems based on nanoparticles obtained from the self-assembly of amphiphilic random poly(l-glutamic acid-co-d-phenylalanine). These P(Glu-co-dPhe) nanoparticles were characterized in terms of their size, surface charge, stability, cytotoxicity, and uptake by macrophages. The encapsulation efficiency and drug loading into P(Glu-co-dPhe) nanoparticles were determined for both polymyxin B and E. The release kinetics of polymyxins B and E from nanoformulations was studied and compared in buffer solution and human blood plasma. The release mechanisms were analyzed using a number of mathematical models. The minimal inhibitory concentrations of the nanoformulations were established and compared with those determined for the free antibiotics.

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Dai, Chongshan, Yang Wang, Gaurav Sharma, Jianzhong Shen, Tony Velkov, and Xilong Xiao. "Polymyxins–Curcumin Combination Antimicrobial Therapy: Safety Implications and Efficacy for Infection Treatment." Antioxidants 9, no. 6 (June 9, 2020): 506. http://dx.doi.org/10.3390/antiox9060506.

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The emergence of antimicrobial resistance in Gram-negative bacteria poses a huge health challenge. The therapeutic use of polymyxins (i.e., colistin and polymyxin B) is commonplace due to high efficacy and limiting treatment options for multidrug-resistant Gram-negative bacterial infections. Nephrotoxicity and neurotoxicity are the major dose-limiting factors that limit the therapeutic window of polymyxins; nephrotoxicity is a complication in up to ~60% of patients. The emergence of polymyxin-resistant strains or polymyxin heteroresistance is also a limiting factor. These caveats have catalyzed the search for polymyxin combinations that synergistically kill polymyxin-susceptible and resistant organisms and/or minimize the unwanted side effects. Curcumin—an FDA-approved natural product—exerts many pharmacological activities. Recent studies showed that polymyxins–curcumin combinations showed a synergistically inhibitory effect on the growth of bacteria (e.g., Gram-positive and Gram-negative bacteria) in vitro. Moreover, curcumin co-administration ameliorated colistin-induced nephrotoxicity and neurotoxicity by inhibiting oxidative stress, mitochondrial dysfunction, inflammation and apoptosis. In this review, we summarize the current knowledge-base of polymyxins–curcumin combination therapy and discuss the underlying mechanisms. For the clinical translation of this combination to become a reality, further research is required to develop novel polymyxins–curcumin formulations with optimized pharmacokinetics and dosage regimens.

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Nation, Roger, Maria Rigatto, Diego Falci, and Alexandre Zavascki. "Polymyxin Acute Kidney Injury: Dosing and Other Strategies to Reduce Toxicity." Antibiotics 8, no. 1 (March 14, 2019): 24. http://dx.doi.org/10.3390/antibiotics8010024.

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Polymyxins are valuable antimicrobials for the management of multidrug-resistant Gram-negative bacteria; however, nephrotoxicity associated with these drugs is a very common side effect that occurs during treatment. This article briefly reviews nephrotoxic mechanisms and risk factors for polymyxin-associated acute kidney injury (AKI) and discusses dosing strategies that may mitigate kidney damage without compromising antimicrobial activity. Polymyxins have a very narrow therapeutic window and patients requiring treatment with these drugs are frequently severely ill and have multiple comorbidities, which increases the risk of AKI. Notably, there is a significant overlap between therapeutic and toxic plasma polymyxin concentrations that substantially complicates dose selection. Recent dosing protocols for both colistin and polymyxin B have been developed and may help fine tune dose adjustment of these antibiotics. Minimizing exposure to modifiable risk factors, such as other nephrotoxic agents, is strongly recommended. The dose should be carefully selected, particularly in high-risk patients. The administration of oxidative stress-reducing drugs is a promising strategy to ameliorate polymyxin-associated AKI, but still requires support from clinical studies.

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Hajimohammadi, Ali, Khalil Badiei, Parviz Kheibari, Meherdad Pourjafar, and Aliasghar Chalmeh. "Effects of polymyxin B on clinical signs, serum TNF-α, haptoglobin and plasma lactate concentrations in experimental endotoxaemia in sheep." Journal of Veterinary Research 62, no. 1 (March 30, 2018): 79–85. http://dx.doi.org/10.2478/jvetres-2018-0011.

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AbstractIntroductionThe experiment evaluated the effects of intravenous administration of polymyxin B on experimental endotoxaemia in sheep.Material and MethodsTwenty clinically healthy fat-tailed sheep were randomly divided into: a group treated with 6,000 U/kg of polymyxin B, a group at 12,000 U/kg, and positive and negative controls. Endotoxaemia was induced by intravenous administration of lipopolysaccharide (LPS) fromE.coliserotype O55:B5 at 0.5 μg/kg. polymyxin was infused intravenously along with 2.5 L of isotonic intravenous fluids at 20 mL/kg/h. The positive control group received LPS and 2.5 L of isotonic fluids, the negatives receiving just 2.5 L of isotonic fluids. Clinical signs were evaluated before and at 1.5, 3, 4.5, 6, 24, and 48 h after LPS administration. Blood was also sampled at the denoted hours and serum haptoglobin, tumour necrosis factor-α (TNF-α), and plasma lactate concentrations were assayed.ResultsThe serum concentration of TNF-α in the positive control group increased significantly up to 48 h after LPS administration. The concentration of TNF-α was significantly different from those of the polymyxin B and positive control groups from 3 to 48 h; also, the concentrations of haptoglobin at different times in the polymyxin groups were lower than those of the positive control group and were significant at hours 3 to 48 (P < 0.05). Following the LPS administration, haptoglobin and TNF-α concentrations changed without significant difference between the two polymyxin B groups.ConclusionPolymyxin B (6,000 U/kg) restrained blood lactate concentrations. Furthermore, it significantly improved the clinical signs in endotoxaemic animals, including rectal temperature and heart and respiratory rates. Polymyxin B may be an antiendotoxic in fat-tailed sheep.

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Tarnate, Paul Sherwin. "Rational Use of Polymyxins Against Multi-Drug Resistant Gram-Negative Bacteria." Pediatric Infectious Disease Society of the Philippines Journal 22, no. 1 (May 21, 2021): 3–13. http://dx.doi.org/10.56964/pidspj2021220102.

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The current strategy in treating multi-drug resistant gram-negative bacterial (MDR-GNB) infections is salvage therapy by using polymyxins. However, the beginning emergence of polymyxin resistance should enforce strict antimicrobial stewardship programs to preserve polymyxin efficacy. Knowledge of structural characteristics, pharmacodynamic, and pharmacokinetic profiles of polymyxins, as well as consideration of efficacy, safety, suitability, and cost, will help in the choice of the appropriate polymyxin for therapy. Polymyxin B is the recommended polymyxin for systemic use, while colistin is recommended for lower urinary tract infections, intraventricular, and intrathecal use. Either polymyxin can be used for hospital-acquired and ventilator-associated pneumonia. Combination therapy over monotherapy remains to be advantageous due to synergism and decreased resistance development. The choice of the second drug to be used should be based on full susceptibility, or if unavailable, a drug with the least minimum inhibitory concentration relative to the breakpoint set by the Clinical and Laboratory Standards Institute. Using the mnemonic ESCAPE can also guide physicians in their polymyxin prescription process: (1) Checking if the pathogen is Extensively resistant or multi-drug resistant; (2) checking the patient’s clinical status if compatible with Significant infection; (3) using Combination therapy; (4) ensuring Adequate dosing; (5) Proper preparation and administration of drug; and (6) keeping an Eye for response and adverse effects.

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Young, J. C., T. G. Kurowski, A. M. Maurice, R. Nesher, and N. B. Ruderman. "Polymyxin B inhibits contraction-stimulated glucose uptake in rat skeletal muscle." Journal of Applied Physiology 70, no. 4 (April 1, 1991): 1650–54. http://dx.doi.org/10.1152/jappl.1991.70.4.1650.

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Glucose transport in muscle is activated by contractile activity, an effect that persists in the postexercise state. Polymyxin B, a cyclic decapeptide antibiotic, inhibits the stimulation of glucose uptake in isolated muscle by contractile activity but also decreases tension development in electrically stimulated muscle. The purpose of this study was to determine whether polymyxin B also inhibits contraction-stimulated glucose uptake after in vivo administration of the drug and to examine the relationship between the effects of polymyxin B on tension development and its effects on contraction-stimulated glucose uptake. When polymyxin B was administered to rats in vivo, glucose uptake in muscle after electrical stimulation was decreased, despite the same amount of tension developed as in control rats, indicating an effect of polymyxin B on glucose transport independent of tension development. Our results also indicate that the postexercise increase in glucose uptake is a function of the tension developed by prior contractions. When muscles were perfused with medium containing polymyxin B, this relationship was disrupted. These results provide evidence that polymyxin B causes a decrease in muscle glucose uptake independent of its effects on tension development. The extent to which its effects on glucose uptake are also the result of a diminution in contractile force is uncertain.

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Alvarado Reyes, Yarelis, Raquel Cruz, Julia Gonzalez, Yeiry Perez, and William R. Wolowich. "Incidence of Acute Kidney Injury in Intermittent Versus Continuous Infusion of Polymyxin B in Hospitalized Patients." Annals of Pharmacotherapy 53, no. 9 (April 11, 2019): 886–93. http://dx.doi.org/10.1177/1060028019841898.

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Background: Studies evaluating the risk of developing acute kidney injury (AKI) with different dosing strategies of polymyxin B are limited. Objectives: To compare the incidence of AKI in patients treated with intermittent versus continuous polymyxin B therapy. Secondary objectives included time to onset of AKI, hospital length of stay (LOS), and all-cause hospital mortality. Variables associated with an increased risk of AKI were evaluated. Methods: A retrospective record review was conducted at a single center in Puerto Rico. Adult patients (≥18 years old) treated with polymyxin B (first course) for at least 48 hours from 2013-2015 were evaluated. Patients with a creatinine clearance <10 mL/min and/or on renal replacement were excluded. Results: A total of 69 patients were included: 42 in the continuous infusion and 27 in the intermittent dosing group. Incidence of AKI was not significantly different between the groups (intermittent 41% vs continuous 31%, P = 0.4). No difference was found in the onset of nephrotoxicity, hospital LOS, or all-cause hospital mortality. Variables associated with increased risk of AKI were baseline serum creatinine, age, and intensive care unit admission. Patients with a body mass index (BMI) >25 kg/m2 on polymyxin B via continuous infusion had a significantly higher cumulative incidence of AKI ( P = 0.016). Conclusion and Relevance: No difference in the risk of polymyxin B nephrotoxicity was found between intermittent and continuous infusion administration. Administration of polymyxin B via a continuous infusion may result in a higher risk of AKI in patients with a BMI >25 kg/m2.

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Neiva, Luciana Barros de Moura, Fernanda Teixeira Borges, Mirian Watanabe, Edson de Andrade Pessoa, Dulce Aparecida Barbosa, and Maria de Fatima Fernandes Vattimo. "Nephrotoxicity Of Polymyxin B: Experimental Study In Cells And Implications For Nursing Practice." Revista da Escola de Enfermagem da USP 48, no. 2 (April 2014): 272–77. http://dx.doi.org/10.1590/s0080-6234201400002000011.

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The aim of the study was to characterize the cell damage mechanisms involved in the pathophysiology of cytotoxicity of polymyxin B in proximal tubular cells (LLC - PK1) and discuss about the nurses interventions to identify at risk patients and consider prevention or treatment of nephrotoxicity acute kidney injury. This is a quantitative experimental in vitro study, in which the cells were exposed to 375μM polymyxin B sulfate concentration. Cell viability was determined by exclusion of fluorescent dyes and morphological method with visualization of apoptotic bodies for fluorescence microscopy. Cells exposed to polymyxin B showed reduced viability, increased number of apoptotic cells and a higher concentration of the enzyme lactate dehydrogenase. The administration of polymyxin B in vitro showed the need for actions to minimize adverse effects such as nephrotoxicity.

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Abdelraouf, Kamilia, Jie He, Kimberly R. Ledesma, Ming Hu, and Vincent H. Tam. "Pharmacokinetics and Renal Disposition of Polymyxin B in an Animal Model." Antimicrobial Agents and Chemotherapy 56, no. 11 (August 20, 2012): 5724–27. http://dx.doi.org/10.1128/aac.01333-12.

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ABSTRACTThe increasing prevalence of multidrug-resistant Gram-negative infections has led to the resurgence of systemic polymyxin B, but little is known about its pharmacokinetics. The objective of this study was to characterize the pharmacokinetics and renal disposition of polymyxin B. Eight female Sprague-Dawley rats (weight, 225 to 250 g) were administered a single intravenous polymyxin B dose (4 mg/kg of body weight). Serial serum samples were collected and assayed for major polymyxin B components using a validated ultraperformance liquid chromatography-tandem mass spectrometry method. The best-fit pharmacokinetic parameters of each component were derived and compared using one-way analysis of variance. Cumulative urine was also collected daily for 48 h and assayed for polymyxin B. Kidney drug concentrations were measured at 6 h (n= 3) and 48 h (n= 3) after the same dose. Additionally, three rats were administered 2 doses of intravenous polymyxin B (4 mg/kg) 7 days apart. Serial serum samples were collected pre- and post-renal insufficiency (induced by uranyl nitrate) and assayed for polymyxin B. The pharmacokinetic parameters of the major components did not appear to be significantly different (P> 0.05). Less than 1% of the dose was recovered unchanged in urine collected over 48 h following administration. Therapeutic drug concentrations persisted in kidney tissue at 48 h. The post-renal insufficiency to pre-renal insufficiency ratio of the area under the serum concentration-time curve from time zero to infinity was 1.33 ± 0.04. Polymyxin B components appear to have similar pharmacokinetics. Polymyxin B preferentially persists in kidneys, which suggests a selective uptake process in renal cells. A mechanism(s) other than renal excretion could be involved in polymyxin B elimination, and dosing adjustment in renal insufficiency may not be necessary.

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Maniara, Bejoy P., Lauren E. Healy, and Thien-Ly Doan. "Risk of Nephrotoxicity Associated With Nonrenally Adjusted Intravenous Polymyxin B Compared to Traditional Dosing." Journal of Pharmacy Practice 33, no. 3 (September 25, 2018): 287–92. http://dx.doi.org/10.1177/0897190018799261.

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Background: Polymyxin B’s package insert recommends renal adjustment. Contemporary studies suggest it does not require renal adjustment. Objective: To determine whether time to acute kidney injury (AKI) differs between renally adjusted and nonadjusted intravenous (IV) polymyxin B. Methods: This retrospective chart review compared time to AKI after renally adjusted and nonadjusted IV polymyxin B administration. It included patients who were 18 years or older, received IV polymyxin B, and had creatinine clearance below 80 mL/min, and excluded ones who had AKI, received renal replacement therapy, or were pregnant. Results: Fifty-four patients were included. There was not any statistical association between dosing type and time to AKI ( P = .13). Incidence of nephrotoxicity, mortality, and length of stay (LOS) were higher in the renally adjusted arm (21.7% vs 6.5%, 17.4% vs 6.5%, and 16 vs 14 days, respectively). Four patients received concomitant ascorbic acid; not one developed AKI. Conclusion: A significant association between IV polymyxin B dosing type and time to AKI was not found. Adverse events were higher in the renally adjusted arm. This suggests that nonadjusted IV polymyxin B may be preferred in patients with renal impairment. Ascorbic acid may mitigate IV polymyxin B's nephrotoxic potential. Further studies are needed to corroborate these findings.

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Mayumi, T., K. Yamada, T. Fukuoka, J. Takezawa, and A. Nakao. "THE EFFECTIVENESS of POLYMYXIN B ADMINISTRATION TO THE OPEATIVE PATIENTS." Shock 15, Supplement (June 2001): 37. http://dx.doi.org/10.1097/00024382-200106001-00111.

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Coppi, Gilberto, Nicoletta Sala, Moreno Bondi, Santo Sergi, and Valentina Iannuccelli. "Ex-vivoevaluation of alginate microparticles for Polymyxin B oral administration." Journal of Drug Targeting 14, no. 9 (January 2006): 599–606. http://dx.doi.org/10.1080/10611860600864182.

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Healan, A. M., W. Gray, E. J. Fuchs, J. M. Griffiss, R. A. Salata, and J. Blumer. "Stability of Colistimethate Sodium in Aqueous Solution." Antimicrobial Agents and Chemotherapy 56, no. 12 (October 15, 2012): 6432–33. http://dx.doi.org/10.1128/aac.01079-12.

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ABSTRACTColistimethate sodium, increasingly used to treat multidrug-resistant Gram-negative infections, spontaneously hydrolyzes to form colistin A (polymyxin E1) and B (polymyxin E2/B) when mixed with water. High levels of these active breakdown products at the time of administration have been associated with nephrotoxicity and even death. In this study, reconstituted colistimethate sodium was shown to be stable (<1.0% colistin A/B formation) for up to 24 h when stored at 21, 0, −20, and −70°C.

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Shinomiya, Shohei, Keisuke Nakase, Ai Fujii, Yutaka Takahara, Hiroki Adachi, Masashi Okuro, Yoshitsugu Iinuma, Hitoshi Yokoyama, Toru Ito, and Shiro Mizuno. "Tocilizumab and PMX-DHP have efficacy for severe COVID-19 pneumonia." SAGE Open Medical Case Reports 9 (January 2021): 2050313X2199106. http://dx.doi.org/10.1177/2050313x21991063.

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In coronavirus disease 2019 pneumonia, a cytokine storm resulting from an excessive inflammatory response to the viral infection is thought to play a role in the exacerbation of the pneumonia and its prognosis. Favipiravir and ciclesonide are not effective in the inhibition of the cytokine storm. In this case report, we describe the experience of tocilizumab administration and polymyxin B immobilized fiber direct hemoperfusion in severe coronavirus disease 2019 pneumonia patient. A 52-year-old man presented with fever and dyspnea and was diagnosed with coronavirus disease 2019 pneumonia based on a polymerase chain reaction test. Mechanical ventilation and favipiravir administration were started for respiratory failure. However, favipiravir could not be continued due to hepatic dysfunction. Consequently, tocilizumab was administered, and continuous hemodiafiltration and endotoxin adsorption therapy (polymyxin B immobilized fiber direct hemoperfusion) were performed for acute renal failure. C-reactive protein decreased from 44 to 3.52 mg/dL, and the patient’s respiratory status improved over time, enabling mechanical ventilation to be withdrawn. This case indicates that adding polymyxin B immobilized fiber direct hemoperfusion to tocilizumab administration may further increase efficacy in coronavirus disease 2019 treatment; however, more case–control studies are needed.

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Stichtenoth, Guido, Marie Haegerstrand-Björkman, Gabi Walter, Bim Linderholm, Egbert Herting, and Tore Curstedt. "Comparison of Polymyxin E and Polymyxin B as an Additive to Pulmonary Surfactant in Escherichia coli Pneumonia of Ventilated Neonatal Rabbits." Biomedicine Hub 2, no. 2 (June 24, 2017): 1–9. http://dx.doi.org/10.1159/000475877.

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Background: Ascending maternofetal bacterial infections often result in premature birth and neonatal respiratory distress. These neonates are treated with exogenous pulmonary surfactant (SF) and systemic antibiotics. Polymyxins are antimicrobiotic peptides that may bind to SF phospholipids. Objectives: Does topical administration of SF/polymyxin reduce bacterial growth in neonatal rabbit pneumonia and improve pulmonary function? Methods: Neonatal rabbits were tracheotomized and treated intratracheally with mixtures of porcine SF, SF/polymyxin E (PxE), or polymyxin B (PxB). Control animals received saline. Animals were then inoculated with Escherichia coli and ventilated for 4 h. During the experiment, peak insufflation pressures, dynamic lung compliance, and ECG were recorded. Pulmonary and renal bacterial load were determined. Lung histology was performed. Lung and kidney IL-8 were measured in subgroups. Results: Eighty-five animals were included in 2 experimental series, of which 78% survived 4 h of ventilation. E. coli inoculation caused severe neonatal pneumonia with median IL-8 levels of 2.2 ng/g in the lungs compared to a median of 0.2 ng/g in the lungs of the saline controls (p < 0.01). Lung compliance after 4 h was significantly increased at a mean of 0.48 ml/(kg·cm H2O) in the SF group and 0.43 in the SF + PxE group compared to 0.35 in the E. coli group (p < 0.01). In direct comparison, bacterial growth found in the E. coli group was reduced 20-fold in the SF + PxB group compared to 75-fold in the SF + PxE group. Conclusion: Addition of polymyxin to SF effectively promotes antimicrobial treatment and improves lung function in neonatal pneumonia of rabbits.

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Mayumi, T., K. Yamada, T. Fukuoka, H. Takahashi, J. Takezawa, and A. Nakao. "PERIOPERATIVE ADMINISTRATION OF POLYMYXIN B SHORTENS HOSPITAL STAY IN SURGICAL PATIENS." Shock 17, Supplement (June 2002): 76. http://dx.doi.org/10.1097/00024382-200206001-00228.

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Mayumi, Toshihiko, Kohjiroh Yamada, Toshio Fukuoka, Hideo Takahashi, Jun Takezawa, Toshiaki Nonami, Seiji Akiyama, and Akimasa Nakao. "The safety and effectiveness of polymyxin B administration to operative patients." Nihon Shuchu Chiryo Igakukai zasshi 6, no. 3 (1999): 229–32. http://dx.doi.org/10.3918/jsicm.6.229.

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Ahmed, Manal Mohamed Elsayed. "Polymyxins: “Last Resort” for MDR and/or XDR Gram-Negative Infections." Journal of Scientific Research in Medical and Biological Sciences 2, no. 3 (August 12, 2021): 104–22. http://dx.doi.org/10.47631/jsrmbs.v2i3.242.

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Polymyxins were used for the management of gram-negative infections in clinical practice science1940s. Parenteral administration waned in the seventies owing to polymyxins nephrotoxicity and neurotoxicity. Because of the lack of treatment choices for MDR and/or XDRgram negative superbugs as well as Acinetobacter baumannii, Klebsiella pneumonia, and Pseudomonas aeruginosa, there is a growing need for effective prescribing of old antibiotics that are still effective. However, understanding of polymyxins pharmacokinetics (PK) was restricted and clinical experience is limited which leads to a lack of widespread availability of up-to-date dosing guidelines that could potentially result in the incorrect use of these “last resort” antibiotics. Recently, polymyxin B resistant strains are also a reason of concern. In this review, we discuss the importance of preserving the effectiveness of polymyxins for nosocomial gram-negative infections and strategies to improve polymyxins’ prescription. We recommend that polymyxins should only be used to manage significant MDR and/or XDRgram-negative infections, in optimum doses and if possible, in combination therapy

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Lin, Hanlu, Xiaobo Liu, and Pengfei Sun. "Effects of Aerosol Inhalation Combined with Intravenous Drip of Polymyxin B on Bacterial Clearance, Symptoms Improvement, and Serum Infection Indexes in Patients with Pneumonia Induced by Multidrug-Resistant Gram-Negative Bacteria." Emergency Medicine International 2022 (August 28, 2022): 1–6. http://dx.doi.org/10.1155/2022/5244538.

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In recent years, the incidence of pneumonia caused by multidrug-resistant (MDR) Gram-negative bacteria (G−) has increased year by year. Polymyxin B has a good clinical effect in the treatment of MDR, but there is controversy about the administration route of this drug. In this study, we retrospectively analyzed the clinical data of 84 cases of MDR Gram-negative bacterial pneumonia, and aimed to explore the effects of aerosol inhalation combined with intravenous polymyxin B infusion on the bacterial clearance, symptom improvement, and serum infection indexes of MDR patients on the patients with Gram-negative (G−) bacterial pneumonia. The results show that aerosol inhalation combined with intravenous drip of polymyxin B can improve bacterial clearance rate, reduce levels of serum inflammatory factors, and improve clinical symptoms in patients with pneumonia induced by MDR G-bacteria.

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Li, Z.-D., J. Luo, L.-H. Jia, X.-Y. Wang, Z.-K. Xun, and M. Liu. "Cytochrome C suppresses renal accumulation and nephrotoxicity of polymyxin B." Human & Experimental Toxicology 38, no. 2 (July 17, 2018): 193–200. http://dx.doi.org/10.1177/0960327118783543.

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The receptor megalin plays an important role in the accumulation of polymyxin B (PMB) in renal cells in vitro. This study aimed to examine the effects of cytochrome c (cyto c), a typical megalin ligand, on renal accumulation and nephrotoxicity of PMB in vivo. Thirty Sprague-Dawley rats were randomly divided into the vehicle control group, PMB group, PMB + cyto c 50, 100, or 200 mg/kg group, respectively, and were treated with intravenous cyto c 30 min before the administration of PMB 4.0 mg/kg once a day for consecutive 5 days. On the 4th day after administration, 24 h urine was collected to determine N-acetyl-β-D-glucosaminidase excretion. Six hours after the last injection on the 5th day, kidneys were harvested to assay PMB concentration and observe pathological alterations, and blood samples were collected to assay serum creatinine (SCr), blood urea nitrogen (BUN), and blood β2-microglobulin (β2-MG) levels. Cyto c 50, 100, and 200 mg/kg decreased the accumulation of PMB in the kidney by 18.5%, 39.1% ( p < 0.01), and 36.8% ( p < 0.01), respectively, and reduced 24 h N-acetyl-β-D- glucosaminidase excretion by 22.5% ( p < 0.05), 40.4% ( p < 0.01), and 40.4% ( p < 0.01), respectively. Kidney pathological damage induced by PMB was markedly reduced by cyto c 100 mg/kg and 200 mg/kg. However, there were no significant differences in SCr, BUN, and blood β2-MG levels among the groups. These results indicated that cyto c may inhibit the renal accumulation and nephrotoxicity of PMB in a rat model, further proving the role of megalin in the accumulation of PMB.

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Morresey, Peter R., and Robert J. MacKay. "Endotoxin-neutralizing activity of polymyxin B in blood after IV administration in horses." American Journal of Veterinary Research 67, no. 4 (April 2006): 642–47. http://dx.doi.org/10.2460/ajvr.67.4.642.

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Wong, David M., Brett A. Sponseller, Cody J. Alcott, Prince N. Agbedanu, Chong Wang, and Walter H. Hsu. "Effects of intravenous administration of polymyxin B in neonatal foals with experimental endotoxemia." Journal of the American Veterinary Medical Association 243, no. 6 (September 15, 2013): 874–81. http://dx.doi.org/10.2460/javma.243.6.874.

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Coppi, G., V. Iannuccelli, N. Sala, and M. Bondi. "Alginate microparticles for Polymyxin B Peyer's patches uptake: microparticles for antibiotic oral administration." Journal of Microencapsulation 21, no. 8 (December 2004): 829–39. http://dx.doi.org/10.1080/02652040400015437.

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Koller, M. E., K. Woie, and R. K. Reed. "Increased negativity of interstitial fluid pressure in rat trachea after mast cell degranulation." Journal of Applied Physiology 74, no. 5 (May 1, 1993): 2135–39. http://dx.doi.org/10.1152/jappl.1993.74.5.2135.

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The present study was performed to investigate whether the increased negativity of interstitial fluid pressure (Pif) observed after intravenous injection of dextran could be mediated via mast cell degranulation induced by C48/80 and polymyxin B sulfate. Increased negativity of Pif, concomitant with edema formation and increased albumin extravasation, was seen with both substances. However, the two substances differed in that polymyxin B sulfate induced less negativity in Pif and a larger but transient increase in capillary albumin extravasation and interstitial fluid volume. Total tissue water (TTW) increased from 2.11 to 2.71 ml/g dry wt 10 min after polymyxin B and returned to control level at 30 and 60 min. Injection of C48/80 increased TTW to 2.68 ml/g dry wt at 30 min, and TTW was still elevated at 60 min. Albumin extravasation followed a similar pattern; polymyxin B sulfate increased albumin extravasation from < 0.08 to 1.18 ml/g dry wt during the first 5 min after administration. C48/80 was less potent, and maximal albumin leakage was seen after 10–25 min (0.25 ml/g dry wt). The observations demonstrate the importance of the interstitium and the loose connective tissues as "active" participants in the edema-generating process and suggest an interaction with the structural components of the interstitium, as well as an important role for the mast cells in the chain of events creating increased negativity of Pif.

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Paterson, David L., Usha Stiefel, and Curtis J. Donskey. "Effect of a Selective Decontamination of the Digestive Tract Regimen Including Parenteral Cefepime on Establishment of Intestinal Colonization with Vancomycin-Resistant Enterococcus spp. and Klebsiella pneumoniae in Mice." Antimicrobial Agents and Chemotherapy 50, no. 7 (July 2006): 2537–40. http://dx.doi.org/10.1128/aac.00071-06.

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ABSTRACT In mice, a selective decontamination of the digestive tract regimen consisting of orogastric tobramycin, polymyxin E, and amphotericin B in combination with subcutaneous cefepime inhibited gram-negative bacilli, including Klebsiella pneumoniae, and did not promote vancomycin-resistant Enterococcus spp. (VRE) colonization. However, concurrent administration of subcutaneous ampicillin-sulbactam resulted in promotion of VRE.

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Kamiya, Hiroyuki, and Ogee Mer Panlaqui. "A systematic review of the efficacy of direct hemoperfusion with a polymyxin B–immobilized fibre column to treat rapidly progressive interstitial pneumonia." SAGE Open Medicine 7 (January 2019): 205031211986182. http://dx.doi.org/10.1177/2050312119861821.

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Objectives: Rapidly progressive interstitial pneumonia is a fatal disease with no established therapeutic options. The aim of this systematic review is to clarify the efficacy of interstitial pneumonia treatment utilizing direct hemoperfusion with a polymyxin B–immobilized fibre column. Methods: All patients with adult-onset rapidly progressive interstitial pneumonia including acute exacerbation of underlying chronic interstitial pneumonia were eligible. Primary studies of any design, which compared outcomes of direct hemoperfusion with a polymyxin B–immobilized fibre column treatment such as oxygenation and all-cause mortality with those of conventional therapy, were included. Electronic databases such as Medline and EMBASE were searched through October 7, 2018, and ICHUSHI, the largest database for medical articles in Japan, was also searched. Two reviewers independently extracted the relevant data and assessed the risk of bias in individual studies. The results were reported qualitatively due to substantial heterogeneity between studies. Results: Out of 775 records retrieved, 10 reports were eligible and 8 of them were included for further analysis. They were all retrospective studies including a total of 327 patients and contained some risk of bias. There was variation in the administration method of direct hemoperfusion with a polymyxin B–immobilized fibre column treatment such as the timing, frequency, duration and interval. Multivariate analyses of only two studies with historical controls demonstrated beneficial effects of direct hemoperfusion with a polymyxin B–immobilized fibre column treatment over conventional therapy with all-cause mortality hazard ratios of 0.345 (95% confidence interval: 0.127–0.936) and 0.505 (95% confidence interval: 0.270–0.904), respectively. A significant difference of an improvement in the ratio of partial arterial oxygen pressure to the fraction of inspired oxygen in-between two treatment groups was also reported in two studies utilizing historical controls with mean differences of 56.8 and 57.5 mmHg, respectively. Conclusions: There is currently insufficient data to support the use of direct hemoperfusion with a polymyxin B–immobilized fibre column treatment for rapidly progressive interstitial pneumonia. It should be instituted for research purposes only until new evidence is available.

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Coppi, G., M. Montanari, T. Rossi, M. Bondi, and V. Iannuccelli. "Cellular uptake and toxicity of microparticles in a perspective of polymyxin B oral administration." International Journal of Pharmaceutics 385, no. 1-2 (January 2010): 42–46. http://dx.doi.org/10.1016/j.ijpharm.2009.10.026.

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Hussein, Maytham, Sara Oberrauch, Rafah Allobawi, Linda Cornthwaite-Duncan, Jing Lu, Rajnikant Sharma, Mark Baker, Jian Li, Gauri G. Rao, and Tony Velkov. "Untargeted metabolomics to evaluate polymyxin B toxicodynamics following direct intracerebroventricular administration into the rat brain." Computational and Structural Biotechnology Journal 20 (2022): 6067–77. http://dx.doi.org/10.1016/j.csbj.2022.10.041.

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Hasan, M. J., and R. Rabbani. "Dual-route-administration versus single-route-administration of polymyxin B in VAP caused by MDR Klebsiella pneumoniae: An observational study." International Journal of Infectious Diseases 101 (December 2020): 130. http://dx.doi.org/10.1016/j.ijid.2020.09.356.

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Kikuchi, Mitsuru, Masatoshi Watanabe, Masaru Ogawa, Ryuji Nakamura, Kazuyoshi Saito, Katsuya Inada, and Masao Yoshida. "The Effects of Oral Administration of Polymyxin B Sulfate and Tinidazol in Patients with Esophageal Varices." Japanese Journal of Gastroenterological Surgery 27, no. 3 (1994): 753–58. http://dx.doi.org/10.5833/jjgs.27.753.

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Moriyama, Naoki, Michio Miyoshi, Toshiaki Imoto, Megumi Maruyama, Osamu Shido, and Tatsuo Watanabe. "Systemic administration of polymyxin B induces hypothermia in rats via an inhibitory effect on metabolic rate." European Journal of Pharmacology 541, no. 1-2 (July 2006): 38–43. http://dx.doi.org/10.1016/j.ejphar.2006.05.006.

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Lim, Tze-Peng, Daryl Kim-Hor Hee, Winnie Lee, Jocelyn Qi-Min Teo, Yiying Cai, Shannon Yu-Hng Chia, Johannesen Yee-Kiat Leaw, Shannon Jing-Yi Lee, Lawrence Soon-U. Lee, and Andrea L. Kwa. "Physicochemical Stability Study of Polymyxin B in Various Infusion Solutions for Administration to Critically Ill Patients." Annals of Pharmacotherapy 50, no. 9 (July 20, 2016): 790–92. http://dx.doi.org/10.1177/1060028016649598.

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Kicielińska, Jagoda, Agnieszka Szczygieł, Joanna Rossowska, Natalia Anger, Katarzyna Kempińska, Marta Świtalska, Marta Kaszowska, Joanna Wietrzyk, Janusz Boratyński, and Elżbieta Pajtasz-Piasecka. "Oral Administration of Polymyxin B Modulates the Activity of Lipooligosaccharide E. coli B against Lung Metastases in Murine Tumor Models." PLOS ONE 11, no. 2 (February 1, 2016): e0148156. http://dx.doi.org/10.1371/journal.pone.0148156.

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Saleem, Ali Faisal, Muhammad Shafaat Shah, Abdul Sattar Shaikh, Fatima Mir, and Anita K. M. Zaidi. "Acinetobacter species meningitis in children: a case series from Karachi, Pakistan." Journal of Infection in Developing Countries 5, no. 11 (November 10, 2011): 809–14. http://dx.doi.org/10.3855/jidc.1697.

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Introduction: Multidrug-resistant strains of Acinetobacter pose a serious therapeutic dilemma in hospital practice, particularly when they cause meningitis, as the few antimicrobial agents to which these isolates are susceptible have poor central nervous system (CNS) penetration. Methodology: We retrospectively reviewed the clinical course and outcome of eight consecutive cases of meningitis due to Acinetobacter spp. in children ages 15 years or less, seen in a tertiary care medical center in Karachi, Pakistan. Results: Of the eight cases of Acinetobacter meningitis, isolates from five patients were pan-resistant, and two were multidrug-resistant. A neurosurgical procedure was performed in five of eight patients followed by external ventricular drain insertion prior to the development of infection. Seven received intravenous (IV) polymyxin (mean; 12.8 days), while 5/8 also received intrathecal (IT) polymyxin (mean; 12.0 days). The mean length of hospitalization was 38.7 ± 19 days. All patients achieved cerebrospinal fluid (CSF) culture negativity by the end of treatment (mean; 5.4 days). Two patients died: one with pan-resistant Acinetobacter, and the second with a multi-drug resistant isolate. Conclusion: Post-neurosurgical multidrug-resistant and pan-resistant Acinetobacter meningitis can be successfully treated if appropriate antimicrobial therapy is instituted early. The role of IT polymyxin B administration alone versus combination therapy (IV and IT) needs further study.

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Drabick, Joseph J., Apurba K. Bhattacharjee, David L. Hoover, George E. Siber, Vivian E. Morales, Lynnette D. Young, Scott L. Brown, and Alan S. Cross. "Covalent Polymyxin B Conjugate with Human Immunoglobulin G as an Antiendotoxin Reagent." Antimicrobial Agents and Chemotherapy 42, no. 3 (March 1, 1998): 583–88. http://dx.doi.org/10.1128/aac.42.3.583.

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ABSTRACT Polymyxin B (PMB) is a cyclic decapeptide antibiotic which also binds and neutralizes endotoxin. Unfortunately, PMB can be considerably nephrotoxic at clinically utilized doses, thereby limiting its utility as a therapeutic antiendotoxin reagent. We sought to change the pharmacokinetics and toxicity profile of PMB by covalently linking it to a human immunoglobulin G (IgG) carrier. Conjugates of PMB with IgG were prepared by EDAC [1-ethyl-3-(3-dimethylaminopropyl) carbodiimide]-mediated amide formation. Analysis by dot enzyme-linked immunosorbent assay with an anti-PMB monoclonal antibody showed that the purified conjugate contained bound PMB. The IgG-PMB conjugate reacted with lipid A and J5 lipopolysaccharide in Western blot assays in a manner comparable to that of whole antiserum with anti-lipid A reactivity; unconjugated IgG had no reactivity. The PMB bound in the conjugate retained its endotoxin-neutralizing activity compared to that of unbound PMB as evidenced by its dose-dependent inhibition of tumor necrosis factor release by endotoxin-stimulated human monocytes in vitro; unconjugated IgG had no activity. By this assay, the PMB-IgG conjugate was determined to have approximately 3.0 μg of bound functional PMB per 100 μg of total protein of conjugate (five molecules of PMB per IgG molecule). The PMB-IgG conjugate was also bactericidal against clinical strains of Escherichia coli,Pseudomonas aeruginosa, and Klebsiella pneumoniae relative to unconjugated IgG with MBCs of <4 μg of conjugate per ml for each of the tested strains. The conjugate appeared to be nontoxic at the highest doses deliverable and provided statistically significant protection from death to galactosamine-sensitized, lipopolysaccharide-challenged mice in a dose-dependent fashion when administered prophylactically 2 h before challenge. However, neither free PMB nor the PMB-IgG conjugate could protect mice challenged with endotoxin 2 h after administration. This suggests that these reagents can play a role in prophylaxis but not in therapy of sepsis. These experiments demonstrated that the PMB-IgG conjugate retains bound yet functional PMB as evidenced by its endotoxin-neutralizing activity both in vitro and in vivo. Further work is required to define the role that this or related conjugate compounds may play in the prophylaxis of endotoxin-mediated disease.

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Schwarz, B., C. Anen, and R. van den Hoven. "Preliminary Data of a Retrospective Study on Neurological Side Effects after Administration of Polymyxin B to Endotoxaemic Horses." Equine Veterinary Journal 45 (September 2013): 18–19. http://dx.doi.org/10.1111/evj.12145_46.

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Melo, Antonio Marlos Duarte de, Ana Beatriz Callou Sampaio Neves, Fabiane Silva Bacellar, Felipe Leite Queiróz de Oliveira, Sandra Regina Prado Lopes, André Bacellar Costa Lima, Diego José Lira Torres, and Liz Marjorie Batista de Freitas Leite. "Hiperpigmentação Cutânea Difusa Induzida por Polimixina B: Um Relato de Caso e Revisão de Literatura / Polymyxin B-Induced Diffuse Cutaneous Hyperpigmentation: A case report and literature review." ID on line. Revista de psicologia 16, no. 60 (May 30, 2022): 794–808. http://dx.doi.org/10.14295/idonline.v16i60.3461.

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Resumo: A polimixina B é um antimicrobiano polipeptídico com atividade bactericida contra bactérias aeróbias gram-negativas, inclusive contra bactérias multirresistentes. A neuro e a nefrotoxicidade são efeitos colaterais consagrados, porém foi observado presença de hiperpigmentação cutânea marrom-acastanhada em face, pescoço, em região posterior do tronco, nádegas e região posterior e proximal dos membros inferiores cinco dias após o início da administração deste antibiótico em uma paciente internada na Enfermaria de Clínica Médica de um hospital do interior do Estado do Ceará. A hiperpigmentação cutânea induzida por Polimixina B é um efeito colateral considerado pouco descrito na literatura médica. Os mecanismos etiopatogênicos que causam esta alteração rara permanecem desconhecidos, mas podem envolver reações de estresse oxidativo, provocando uma liberação de histamina, que tem efeito melanogênico, culminando com a deposição de melanina na derme. Ainda que não seja um efeito adverso com risco de vida, a hiperpigmentação cutânea pode gerar danos estéticos importantes, além de distúrbios psicológicos, porém várias questões a respeito dessa reação permanecem obscuras, como possíveis terapêuticas que poderiam ser utilizadas e prognóstico. Diante disso, o objetivo deste Trabalho foi relatar um caso de hiperpigmentação cutânea induzida por Polimixina B em paciente internada no setor de Enfermaria de Clínica Médica em um hospital do interior do Estado do Ceará, além de revisar a literatura sobre o mesmo assunto. Para isso, foi realizada uma busca ativa dos dados clínico-epidemiológicos e socioambientais presentes nos arquivos do hospital em questão, no prontuário da paciente, além de busca e leitura de periódicos nas bases de dados PubMed e SciELO no ano de 2022.Palavras-chave: Hiperpigmentação cutânea; Polimixina B. Abstract: Polymyxin B is a polypeptide antimicrobial with bactericidal activity against aerobic gram-negative bacteria, including multidrug-resistant bacteria. Neurotoxicity and nephrotoxicity are consecrated side effects, but brown-brown cutaneous hyperpigmentation was observed on the face, neck, posterior region of the trunk, buttocks and posterior and proximal regions of the lower limbs five days after the beginning of the administration of this antibiotic in a patient hospitalized in the Internal Medicine Infirmary of a hospital in the interior of the State of Ceará. Polymyxin B-induced cutaneous hyperpigmentation is a side effect considered to be poorly described in the medical literature. The etiopathogenic mechanisms that cause this rare alteration remain unknown, but they may involve oxidative stress reactions, causing a release of histamine, which has a melanogenic effect, culminating in the deposition of melanin in the dermis. Although not a life-threatening adverse effect, cutaneous hyperpigmentation can cause significant aesthetic damage, in addition to psychological disorders, but several questions regarding this reaction remain unclear, such as possible therapies that could be used and prognosis. Therefore, the objective of this work was to report a case of cutaneous hyperpigmentation induced by Polymyxin B in a patient admitted to the Internal Medicine Infirmary in a hospital in the interior of the State of Ceará, in addition to reviewing the literature on the same subject. For this, an active search was carried out for the clinical-epidemiological and socio-environmental data present in the files of the hospital in question, in the patient's chart, in addition to searching and reading journals in the PubMed and SciELO databases in the year 2022.Keywords: Skin hyperpigmentation; Polymyxin B.

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Kabir, M. Shahjahan, Ying-Hsin Hsieh, Steven Simpson, Khalil Kerdahi, and Irshad M. Sulaiman. "Evaluation of Two Standard and Two Chromogenic Selective Media for Optimal Growth and Enumeration of Isolates of 16 Unique Bacillus Species." Journal of Food Protection 80, no. 6 (May 3, 2017): 952–62. http://dx.doi.org/10.4315/0362-028x.jfp-16-441.

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ABSTRACTThe genus Bacillus is a group of gram-positive endospore-forming bacteria that can cause food poisoning and diarrheal illness in humans. A wide range of food products have been linked to foodborne outbreaks associated with these opportunistic pathogens. The U.S. Food and Drug Administration recommends (in their Bacteriological Analytical Manual) the use of Bacara or mannitol egg yolk polymyxin (MYP) agar plates and the most-probable-number (MPN) method for enumeration and confirmation of Bacillus cereus and related species isolated from foods, sporadic cases, outbreaks, and routine environmental surveillance samples. We performed a comparative analysis of two chromogenic media (Bacara and Brilliance) and two traditional media (MYP and polymyxin egg yolk mannitol bromothymol blue agar [PEMBA]) for the isolation and enumeration of 16 Bacillus species under modified growth conditions that included pH, temperature, and dilution factor. A total of 50 environmental, food, and American Type Culture Collection reference isolates from 16 distinct Bacillus species were evaluated. A food adulteration experiment also was carried out by artificially adulterating two baby food matrices with two isolates each of B. cereus and Bacillus thuringiensis. Our results clearly indicated that chromogenic plating media (Bacara and Brilliance) are better than conventional standard media (MYP and PEMBA) for the detection and enumeration of B. cereus in foods and other official regulatory samples. The comparison of the two chromogenic media also indicated that Brilliance medium to be more efficient and selective for the isolation of Bacillus.

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Yoshino, Shin, Eizaburo Sasatomi, Yoki Mori, and Masaru Sagai. "Oral Administration of Lipopolysaccharide Exacerbates Collagen-Induced Arthritis in Mice." Journal of Immunology 163, no. 6 (September 15, 1999): 3417–22. http://dx.doi.org/10.4049/jimmunol.163.6.3417.

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Abstract We investigated whether oral administration of LPS exacerbated collagen-induced arthritis (CIA) in mice, which was an experimental model of autoimmune disease. CIA was induced by s.c. injection of type II collagen emulsified with CFA into the base of the tail (day 0) followed by a booster injection on day 21. To examine the ability of LPS to exacerbate CIA, varying doses of LPS were orally administered on day 50. The results showed that administration of LPS was followed by reactivation of CIA in a dose-related fashion. Histologically, on day 55 there were marked edema of synovium proliferated by day 50, new formation of fibrin, and intense infiltration of neutrophils accompanied with a large number of mononuclear cells. Severe destruction of cartilage and subchondral bone was also observed on day 70. The reactivation of CIA by oral administration of LPS was associated with increase in anti-type II collagen IgG and IgG2a Abs as well as varying kinds of cytokines including IL-12, IFN-γ, IL-1β, and TNF-α. Polymyxin B sulfate given either orally or i.v. suppressed the recurrence of CIA. Increased amounts of LPS were found in sera of mice given the endotoxin orally. LPS from Salmonella enteritidis, Salmonella typhimurium, and Klebsiella pneumoniae and its component, lipid A from Escherichia coli, also reactivated the disease. These findings suggest that LPS from intestinal bacteria may play a role in the exacerbation of autoimmune joint inflammation.

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Truong, Cong Bang, Spencer H. Durham, and Jingjing Qian. "Comparisons of adverse event reporting for colistin versus polymyxin B using the US Food and Drug Administration Adverse Event Reporting System (FAERS)." Expert Opinion on Drug Safety 20, no. 5 (February 22, 2021): 603–9. http://dx.doi.org/10.1080/14740338.2021.1890024.

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Kulengowski, Brandon, Justin A. Clark, and David S. Burgess. "Staggering the administration of polymyxin B and meropenem in time-kill against carbapenem-resistant Enterobacteriaceae exhibiting a wide range of meropenem MICs." Diagnostic Microbiology and Infectious Disease 93, no. 3 (March 2019): 261–64. http://dx.doi.org/10.1016/j.diagmicrobio.2018.09.014.

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Speekenbrink, A. B. J., S. R. Alcock, J. Forrester, and D. M. V. Parrott. "The effect of selective decontamination of the digestive tract with the addition of systemic cefotaxime on the aerobic faecal flora of mice." Epidemiology and Infection 98, no. 3 (June 1987): 385–95. http://dx.doi.org/10.1017/s0950268800062154.

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SUMMARYThe administration per-orally to mice of the non-absorbable antibiotics polymyxin E, tobramycin and amphotericin B resulted in the elimination of detectable aerobic gram-negative rods from the faecal flora without affecting the total viable aerobic count. The addition of parental cefotaxime to the regime caused a fall in the number of aerobic lactobacilli and an increase in the number of enterococci. The rise was associated with the translocation of viable enterococci to the mesenteric lymph nodes and the spleen. The changes induced by cefotaxime were reversed when the antibiotic was withdrawn. Following withdrawal of all antibiotics the total aerobic faecal flora increased to above normal levels, but there was no associated diarrhoea. Attempts to implant exogenous enterobacteria into the digestive tract resulted in only low level colonization both in treated mice and in control mice. These results may have implications for the use of this antibiotic regime for selective decontamination of the digestive tract in humans, particularly those who are immunocompromised.

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Kasai, H., L. M. He, M. Kawamura, P. T. Yang, X. W. Deng, M. Munkanta, A. Yamashita, et al. "IL-12 Production Induced byAgaricus blazeiFraction H (ABH) Involves Toll-like Receptor (TLR)." Evidence-Based Complementary and Alternative Medicine 1, no. 3 (2004): 259–67. http://dx.doi.org/10.1093/ecam/neh043.

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Agaricus blazeiMurill is an edible fungus used in traditional medicine, which has various well-documented medicinal properties. In the present study, we investigated the effects of hemicellulase-derived mycelia extract (Agaricus blazeifraction H: ABH) on the immune system. First, we examined the cytokine-inducing activity of ABH on human peripheral mononuclear cells (PBMC). The results indicated that ABH induced expression of IL-12, a cytokine known to be a critical regulator of cellular immune responses. Flow cytometric analysis demonstrated the induction of IL-12 production by the CD14-positive cell population, consisting of monocytes/macrophages (Mo/Mφ). Furthermore, the elimination of Mo/Mφ attenuated IL-12 production in PBMC. ABH-induced IL-12 production was inhibited by anti-CD14 and anti-TLR4 antibodies but not by anti-TLR2 antibody. The activity of ABH was not inhibited by polymyxin B, while the activity of lipopolysaccharide used as a reference was inhibited. Oral administration of ABH enhanced natural killer (NK) activity in the spleen. These findings suggest that ABH activated Mo/Mφ in a manner dependent on CD14/TLR4 and NK activity.

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Bandhauer, Florian, Daniela Buhl, and Rudolf Grossenbacher. "Antibiotic Prophylaxis in Rhinosurgery." American Journal of Rhinology 16, no. 3 (May 2002): 135–39. http://dx.doi.org/10.1177/194589240201600302.

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Background This study investigated the in vivo efficacy of nasal packing containing an antibiotic substance after septal and turbinate surgery on the potentially infectious nasal flora (Staphylococcus aureus, etc.) without systemic administration of antibiotics. Methods The study was designed as an exploratory randomized trial. Three types of packings were used on 110 patients because of septoplasty and/or turbinate surgery. Packings were distributed randomly among three groups. The first and second groups received an antibiotic-free sample (polyvinyl acetate sponge and cotton gauze strips with sea-salt ointment) and the third group received an antibiotic one (cotton gauze strips with polymyxin-B-sulfate and oxytetracycline ointment). The nasal flora was determined by microscopy and cultures, both preoperatively and after elimination of the packing. Results Significantly less growth of the potentially infectious nasal flora overall and of S. aureus in particular was found in the group with the antibiotic packing. Conclusion Antibiotic-containing nasal packing effectively inhibits potentially infectious germs (including S. aureus) in the nasal flora and secondarily may diminish the incidence of postoperative infections.

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Gysembergh, A., H. Margonari, J. Loufoua, A. Ovize, X. André-Fouët, Y. Minaire, and M. Ovize. "Stretch-induced protection shares a common mechanism with ischemic preconditioning in rabbit heart." American Journal of Physiology-Heart and Circulatory Physiology 274, no. 3 (March 1, 1998): H955—H964. http://dx.doi.org/10.1152/ajpheart.1998.274.3.h955.

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We sought to determine whether stretch-induced preconditioning may be related to activation of adenosine receptors, ATP-sensitive K+([Formula: see text]) channels, and/or protein kinase C (PKC) in the rabbit heart. Anesthetized rabbits underwent 30 min of coronary artery occlusion followed by 3 h of reperfusion. Ischemic preconditioning was induced by one episode of 5 min of ischemia followed by 5 min of reperfusion, and stretch preconditioning was induced by a transient volume overload. The abilities of gadolinium (Gd3+), a blocker of stretch-activated channels, glibenclamide (Glib), a blocker of [Formula: see text] channels, 8-( p-sulfophenyl)-theophylline (8-SPT), a blocker of adenosine receptors, and polymyxin B (PMXB), an antagonist of PKC, to prevent the infarct size-limiting effect of stretch-induced preconditioning were evaluated. Because the infarct size-reducing effect of stretch occurred in the absence of ischemia and was prevented by previous administration of Gd3+, Glib, 8-SPT, and PMXB, we propose that activation of mechanosensitive ion channels protects the rabbit heart from subsequent sustained ischemic insult, likely through a mechanism that involves downstream activation of PKC, adenosine receptors, and/or [Formula: see text] channels.

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Eriguchi, Yoshihiro, Shuichiro Takashima, Hideyo Oka, Sonoko Shimoji, Kiminori Nakamura, Hidetaka Uryu, Shinji Shimoda, et al. "Graft-versus-host disease disrupts intestinal microbial ecology by inhibiting Paneth cell production of α-defensins." Blood 120, no. 1 (July 5, 2012): 223–31. http://dx.doi.org/10.1182/blood-2011-12-401166.

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AbstractAllogeneic hematopoietic stem cell transplantation (SCT) is a curative therapy for various hematologic disorders. Graft-versus-host disease (GVHD) and infections are the major complications of SCT, and their close relationship has been suggested. In this study, we evaluated a link between 2 complications in mouse models. The intestinal microbial communities are actively regulated by Paneth cells through their secretion of antimicrobial peptides, α-defensins. We discovered that Paneth cells are targeted by GVHD, resulting in marked reduction in the expression of α-defensins, which selectively kill noncommensals, while preserving commensals. Molecular profiling of intestinal microbial communities showed loss of physiologic diversity among the microflora and the overwhelming expansion of otherwise rare bacteria Escherichia coli, which caused septicemia. These changes occurred only in mice with GVHD, independently on conditioning-induced intestinal injury, and there was a significant correlation between alteration in the intestinal microbiota and GVHD severity. Oral administration of polymyxin B inhibited outgrowth of E coli and ameliorated GVHD. These results reveal the novel mechanism responsible for shift in the gut flora from commensals toward the widespread prevalence of pathogens and the previously unrecognized association between GVHD and infection after allogeneic SCT.

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Baul, Shuvra Neel, Rajib De, PRAKAS KUMAR MANDAL, Swagnik Roy, Tuphan Kanti Dolai, and Prantar Chakrabarti. "OUTBREAK OF BURKHOLDERIA CEPACIA INFECTION: A SYSTEMATIC STUDY IN A HEMATOLOGY-ONCOLOGY UNIT OF A TERTIARY CARE HOSPITAL FROM EASTERN INDIA." Mediterranean Journal of Hematology and Infectious Diseases 10, no. 1 (September 1, 2018): e2018051. http://dx.doi.org/10.4084/mjhid.2018.051.

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Background: Burkholderia cepacia, an aerobic gram-negative bacillus, is a frequent colonizer of fluids used in the hospital ward. It poses little risk of infection to healthy people; however it is a known important opportunistic pathogen causing morbidity and mortality due to its intrinsic resistance to most of the antibiotics in hospitalized patients. Small hospital outbreaks are frequent. B. cepacia may occur as an opportunistic infection in hemato-oncology patients. Here we present an outbreak of Burkholderia cepacia infection in hematology ward of our institute.Methods: Febrile episodes as defined by IDSA guideline, 2010 were followed, and blood for culture and sensitivity was sent in all the events. The culture was done by an automated method using Bactalert 3d Biomeriux & sensitivity pattern by Microscan Siemens method and subsequently detected by PCR based method.Results: During September 2016 to February 2017 (six months), a total of 498 blood cultures were sent during febrile episodes. Out of which 60 (12%) came out to be positive for different microorganisms. Out of all positive cultures, Burkholderia cepacia was detected in 29 (48%) patients, which reduced drastically following the change in antibiotic administration practice. All isolates showed sensitivity to pipercillin+tazobactum, cefoperazone+sulbactum, fluoroquinolones, cotrimoxazole and carbapenems and resistance to polymyxin B and colistin. With timely intervention by appropriate intravenous antibiotics as per culture sensitivity result and change in antibiotic preparation practice, overall mortality was low 1 (4%) out of 29 culture positive episodes.

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Ewald, Margaret M., Amy J. Rankin, Jessica M. Meekins, Geraldine Magnin, and Butch KuKanich. "Prednisolone and dexamethasone are systemically absorbed after topical application of ophthalmic suspensions in healthy dogs." American Journal of Veterinary Research 83, no. 4 (April 1, 2022): 339–48. http://dx.doi.org/10.2460/ajvr.21.04.0059.

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Abstract OBJECTIVE To quantify plasma concentrations of prednisolone and dexamethasone (peripheral and jugular) and cortisol following topical ophthalmic application of 1% prednisolone acetate and 0.1% dexamethasone to healthy adult dogs. ANIMALS 12 purpose-bred Beagles. PROCEDURES Dogs received 1 drop of 1% prednisolone acetate (n = 6) or neomycin polymyxin B dexamethasone (ie, 0.1% dexamethasone; 6) ophthalmic suspension in both eyes every 6 hours for 14 days. Blood samples (peripheral and jugular) were collected on days 0, 1, 7, and 14 and analyzed for plasma prednisolone and dexamethasone concentrations. Plasma cortisol concentrations were measured at the beginning of the study and following topical drug administration. RESULTS Both drugs demonstrated systemic absorption. Prednisolone was detected on days 1, 7, and 14 (median plasma concentration, 24.80 ng/mL; range, 6.20 to 74.00 ng/mL), and dexamethasone was detected on days 1, 7, and 14 (2.30 ng/mL; 0 to 17.70 ng/mL). Neither prednisolone nor dexamethasone were detected in plasma samples on day 0 (baseline). Sampling from the jugular vein resulted in higher plasma drug concentrations than from a peripheral vein when samples from each day were combined. Plasma cortisol concentrations were significantly lower than baseline following 14 days of treatment with topical prednisolone acetate and dexamethasone. CLINICAL RELEVANCE Prednisolone and dexamethasone are detected in the plasma of healthy dogs following topical ophthalmic administration 4 times/d with prednisolone concentrations being close to a physiologic dose of orally administered prednisolone. Additional research is needed to evaluate the systemic absorption of these medications in dogs with ocular inflammation.

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Yossa, Nadine, Son T. Hoang, Travis Canida, Rebecca Bell, Sandra Tallent, Eric Brown, and Thomas Hammack. "Comparison of Different Culture Methods for the Detection of Bacillus cereus Group in Cosmetics." Journal of AOAC INTERNATIONAL 103, no. 4 (June 30, 2020): 1129–39. http://dx.doi.org/10.1093/jaoacint/qsaa016.

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Abstract Background The U.S. Food and Drug Administration (FDA) Bacteriological Analytical Manual (BAM) reference culture method uses Modified Letheen Broth (MLB) for microbiological analyses for all types of cosmetic products. Objective This study evaluated the effectiveness of MLB and Tryptone Azolectin Tween (TAT) broths using BAM reference culture method for cosmetics. Methods Pure spore suspensions of B. cereus group members were experimentally spiked (McF: 0.5) into cosmetic products. After an aging period of 72 h, the products were analyzed using MLB and TAT broth. The enumeration of the cells was performed on B. cereus group selective plates Bacillus cereus rapid agar (BACARA) and Mannitol Yolk Polymyxin (MYP) plates. Results No statistical difference (p > 0.05) was found for the recovery of cells from the liquid products using either medium (MLB or TAT broth) and the selective plates. In solid/powder products, a combination of Tween 80 and MLB detected significantly more cells (p < 0.05) than combination of Tween 80 and TAT broth. The microbial counts on BACARA showed no significant differences (p > 0.05). However, when assessing cream/oil-based products, the number of cells detected by use of Tween 80/TAT broth was significantly higher than Tween 80/MLB, and MYP showed significantly higher counts than BACARA. Conclusions This study showed that relative effectiveness of MLB vs. TAT for recovering of B. cereus group cells varied depending on the variety of formulation, and combination of preservatives of the tested cosmetic products. The findings suggest additional studies are needed to explore recovery of other relevant microorganisms that may contaminate cream/oil-based cosmetics.

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Journal articles on the topic 'Polymyxin B administration'

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